1. Field of the Invention
This invention relates to a novel peptide derivative, exhibiting endothelin receptor antagonistic action, which is pharmaceutically useful as, for example, a therapeutic or prophylactic agent of cardio- or cerebro-circulatory disease, hepatic disease and/or renal disease, a method of producing it, and a pharmaceutical composition containing the compound.
2. Description of Related Art
Endothelin (ET) is a vasoconstricting peptide consisting of 21 amino acids, which was isolated from the supernatant of swine arterial endothelial culture and structurally determined by Yanagisawa et al. Yanagisawa et al.: Nature, Vol. 332, pp.411-415 (1988)!. Endothelin was later found to exhibit a variety of actions, and endothelin antibodies as endothelin antagonists have proven effective in the treatment of myocardial infarction, renal failure and other diseases. Since endothelin is present in living bodies and exhibits vasoconstricting action, it is be an endogenous factor involved in the regulation of the circulatory system and has an association with hypertension, cardio- or cerebro-vascular diseases, e.g. myocardial infarction: and renal diseases, e.g. acute renal failure: and hepatic diseases, e.g. hepatargia. Since it also exhibits bronchial smooth muscle constricting action, it has an association with asthma.
While, as endothelin antagonists, there have recently been disclosed peptides exhibiting endothelin antagonistic action in JP-A 107680/1994 and Bioorganic & Medicinal Chemistry Letters, Vol. 5, pp.1483 (1995), those exhibiting actions are not sufficient.